DESCRIPTION: (abstract provided by the applicant): The past 20 years of stroke research have shown that acute stroke is a treatable disease but reversibility of damage is tightly time dependent. It is possible to find exciting treatment strategies in the laboratory, but difficult to design and carry out clinical research to translate them into clinical benefit. Even when effective therapy is demonstrated, there are unexpectedly huge impediments to having it adopted and widely available. Given the massive public health problem of stroke in our aging population, these conundrums demand our attention. They are the foci of the UT Stroke Program and the SPOTRIAS PA. The thematic model of our Stroke Program is to develop improved treatment of acute stroke by 1) laboratory investigation into the biology of stroke, 2) clinical investigation of new therapies based on these laboratory studies, and 3) assessment of outcome and improved application of effective therapies. This Program Project has three broad Specific Aims: 1. Development of effective new acute stroke therapies through clinical research projects based on biological principles of ischemic injury learned in the laboratory. We will describe four planned Phase 1 or 2 Clinical trials of novel acute interventions; caffeinol for neuroprotection, the thrombin inhibitor argatroban to enhance reperfusion after TPA, ultrasound to augment clot lysis after TPA, and constraint induced movement therapy to amplify recovery. These projects require the multidisciplinary involvement of EMS, Emergency Medicine, Radiology, Critical Care, Ultrasound, and Rehabilitation. 2. Application of more efficient and widespread acute stroke treatment by improving the organization of local and regional stroke centers using cutting-edge telemedicine technology, and evaluation of a novel middle-school educational initiative to help solve the problem of inadequate public knowledge. 3. Development of Clinical, Statistical, Human Tissue, and Training "Cores" that will facilitate the accomplishment of Specific Aims # 1 and 2. These cores will also provide important new resources for fellowship training.